 This study developed and improved sustained release, SR, poly, lactic-coglycolic acid, PLGA, microsphere of exonetide using supercritical fluid extraction of emulsion, SFE. The study used a box-banking design, BBD, to optimize the process parameters of SFE, which included pressure, temperature, stirring rate, and flow ratio. The resulting microspheres had a smaller particle size, lower initial burst release, and lower residual solvents when compared to microspheres produced via conventional solvent evaporation, SE. In addition, the microspheres showed improved pharmacological activity in terms of reducing blood glucose levels, weight gain, and food intake. Overall, the study demonstrated the potential of SFE to improve the properties of injectable SR-PLGA microspheres. This article was authored by Hee Joon Park, Eun Sol Ha, Jong Soo Kim, and others.